In the following discussion certain articles and processes will be described for background and introductory purposes. Nothing contained herein is to be construed as an “admission” of prior art. Applicant expressly reserves the right to demonstrate, where appropriate, that the articles and processes referenced herein do not constitute prior art under the applicable statutory provisions.
An individual's genetic profile plays an important role in determining risk for disease and response to medical therapy. The development of technologies that facilitate rapid whole-genome sequencing will provide unprecedented power in the estimation of disease risk. Improvements in sequencing technology have enabled cost effective generation of whole genome sequences for individuals. By combining whole genome sequence information with family or pedigree information or with longer sequencing read technology, one may also now phase genomes. A phased genome will describe which variants are aggregated together within chromosomal regions for a particular individual. The interrogation of the entire phased genome provides superior sensitivity to linked genetic features and identification of recombination events.
It has been long recognized that certain sources of biological samples from a pregnant mammal (e.g., blood or plasma), contains DNA from both the mother and the fetus. This recognition has led to the use of maternal samples to identify, non-invasively to the fetus, fetal genetic characteristics, including qualitative (e.g., sex determination and RhD status) and quantitative (fetal copy number variations including trisomies) genetic detection of fetal sequences (for review see, e.g., Lo et al., October 2011). It has also been demonstrated by deep sequencing of the cell-free DNA in a maternal sample that sequences representative of the entire fetal genome is present in circulation. (Lo Y-M et al., Sci Transl Med. 2010 Dec. 8; 2(61):61ra91.) However, the percent fetal DNA is usually present in a low amount, usually 3-40%. Although deep, whole-genome sequencing of the fetal genome has been performed, with conventional technologies this approach is at present economically infeasible for widespread clinical or commercial use.
Thus, improved processes and systems for the identification of inherited alleles in a fetus from a maternal sample would be of great benefit in the art. The present invention addresses this need.